Reduction and Coupling Reactions of Carbonyl Compounds Using Samarium Metal in Aqueous Media

Direct use of metallic Sm as a reducing agent in organic transformations has drawn chemists’ attention.1 Such reactions are generally performed in THF. For example, alkyl iodides are reduced to alkanes by Sm in THF.2a Barbier reaction of 2-(3-iodopropyl)cycloheptanone with Sm in THF occurs intramolecularly to give a bicyclic alcohol.2b Iodomethylations of carbonyl compounds are achieved by treatment with Sm and CH2I2 in THF.2c Since water is an environmentally benign medium, we wish to explore further the reactions of carbonyl compounds with Sm in aqueous media.3 Sm is quite stable in water even though it has a high reduction potential (Sm3+/Sm ) -2.41 V).4 There are several methods2,5 for activation of Sm metal such as amalgamation using I2, HCl, and alkyl halides. Cyclopropanations of esters, R-halo ketones, and allylic alcohols are realized by using Sm(Hg)/ICH2Cl or Sm/ HgCl2/ICH2Cl in THF.2d,e Sm with a catalytic amount of I2 in THF is used in the reductive coupling reactions of N-alkylideneanilines, giving vicinal diamines.2f Deoxygenative coupling reactions of benzamides, giving 1,2diaminostilbenes, are carried out by using Sm with a catalytic amount of SmI2 in THF.2g A minute amount of water is found to accelerate the pinacolic coupling reactions of aromatic carbonyl compounds mediated by Sm/ Me3SiCl in THF.5a Reductions of nitrobenzene,5b 1,2dibromoalkanes,5c,d benzoic acid derivatives,5e and pyridines5f have been realized by using Sm/I2 or Sm/HClaq in MeOH. Pinacolic coupling reactions of aromatic ketones have been achieved by using Sm with alkyl halides in MeOH.5g The expected Barbier-type addition products are not found.5g Our study was initiated by examining the reactivity of 4-bromobenzaldehyde (1b) with Sm in aqueous media (Table 1). The Sm ingot was abraded (by a file) to give shining powders for the present study. Treatment of 1b with Sm (1.2 molar proportions) in H2O/THF (5:1) for 72 h afforded very low yields of pinacol 2b (3%) and alcohol 3b (2%) accompanied by a 95% recovery of 1b. The residual Sm had tarnished by the end of the reaction. The reaction was not significantly improved by sonication or by using an excessive amount of Sm (entries 2 and 3, Table 1). We thus searched for appropriate activators to enhance the reactivity of Sm in aqueous media.2,5,6 Indeed, treatment of 1b with Sm (3 molar proportions) in the presence of HgCl2 (1.5 molar proportions) gave much higher yields of pinacol 2b (48%) and alcohol 3b (38%) in H2O/THF media (entry 4, Table 1). Iodine was also an effective activator of Sm (entries 6-8).2f By using Sm (3 molar proportions) with I2 (0.75 molar proportions), 1b was completely converted in 16 h to give equal amounts of 2b and 3b. Preferable formation of pinacol 2b over alcohol 3b was realized by using Sm in saturated NH4Cl/THF (5:1) or with FeCl3 activation (entries 9 and 10, Table 1). The bromine atom of 1b was retained in all of these reaction conditions. After a comprehensive survey on the optimization of reaction conditions, we found that the reaction in aqueous HCl solution (2 M)5d-f produced an 88% yield of pinacol 2b in a chemoselective manner (entry 12, Table 1). Thus, Sm (3 molar proportions) was added in several portions to a suspension of 1b (1 mmol) in 2 M HCl/THF (5:1) over a period of 1 h at room temperature. Upon addition of Sm powders, a transient purple color and hydrogen evolution were observed. The reaction mixture was continuously stirred without rigorous exclusion of oxygen. It required 32 h for the consumption of 4-bromobenzaldehyde as shown by TLC analyses. The media became transparent at the end of the reaction, and no residue of Sm particles remained. The reaction did not proceed to completion if the amount of Sm was less than 1.2 molar proportions. A considerable portion of starting material 1b was recovered if the reaction was conducted by addition of aqueous HCl solution to the suspension of 1b and Sm in THF (entry 13, Table 1). The reaction in aqueous HBr was less chemoselective (entry 14, Table * To whom correspondence should be addressed. Fax: (886-2)2363-6359. (1) (a) Kagan, H. B.; Namy, J. L. Tetrahedron 1986, 42, 6573. (b) Molander, G. A.; Harris, C. R. In Encyclopedia of Reagents for Organic Synthesis; Paquette, L. A., Ed.; Wiley: Chichester, 1995; Vol. 6, p 4425. (2) (a) Ogawa, A.; Nanke, T.; Takami, N.; Sumino, Y.; Ryu, I.; Sonoda, N. Chem. Lett. 1994, 379. (b) Molander, G. A.; Etter, J. B. J. Org. Chem. 1986, 51, 1778. (c) Imamoto, T.; Takeyam, T.; Koto, H. Tetrahedron Lett. 1986, 27, 3243. (d) Imamoto, T.; Kamiya, Y.; Hatajima, T.; Takahashi, H. Tetrahedron Lett. 1989, 38, 5149. (e) Molander, G. A.; Etter, J. B. J. Org. Chem. 1987, 52, 3942. (f) Yanada, R.; Negoro, N.; Okaniwa, M.; Miwa, Y.; Taga, T.; Yanada, K.; Fujita, T. Synlett 1999, 537. (g) Ogawa, A.; Takami, N.; Sekiguchi, M.; Ryu, I.; Kambe, N.; Sonoda, N. J. Am. Chem. Soc. 1992, 114, 8729. (3) Zn, In and Sn metals are often operative in aqueous media. For reviews, see: (a) Li, C. J.; Chan, T. H. Organic Reactions in Aqueous Media; Wiley: New York, 1997. (b) Chan, T. H.; Li, C. J.; Lee, M. C.; Wei, Z. Y. Can. J. Chem. 1994, 72, 1181. (c) Li, C. J. Tetrahedron 1996, 52, 5643. (d) Lubineau, A.; Auge, J.; Queneau, Y. Synthesis 1994, 741. (4) For the reduction potential and stability of Sm in water. See: (a) Moeller, T. In Comprehensive Inorganic Chemistry; Bailar, J. C., Emeleus, H. J., Nyholm, R., Trotman-Dickenson, A. F., Eds.; Pergamon Press: Oxford, 1973; Vol. 4, p 5. (b) Latimer, W. M. The Oxidation States of the Elements and Their Potentials in Aqueous Solution, 2nd ed.; Prentice Hall Inc.: Englewood Cliffs, NJ, 1952; p 340. (5) (a) Wang, L.; Zhang, Y. Tetrahedron 1998, 54, 11129. (b) Banik, B. K.; Mukhopadhyay, C.; Venkatraman, M. S.; Becker, F. F. Tetrahedron Lett. 1998, 39, 7243. (c) Yanada, R.; Negora. N.; Yanada, K.; Fujita, T. Tetrahedron Lett. 1997, 38, 3271. (d) Yanada, R.; Bessho, K.; Yanada, K. Chem. Lett. 1994, 1279. (e) Komachi, Y.; Kudo, T. Chem. Pharm. Bull. 1994, 42, 402. (f) Komachi, Y.; Kudo, T. Chem. Pharm. Bull. 1995, 43, 1422. (g) Ghatak, A.; Becker, F. F.; Banik, B. K. Tetrahedron Lett. 2000, 41, 3793. (6) General methods for activation of metals, see: (a) Cintas, P., Activated Metals in Organic Synthesis; CRC Press: Boca Raton, 1993. (b) Furstner, A. Active Metals Preparation, Characterization and Application; VCH: Weinheim, 1996. For activation of Sm by ICH2CH2I, I2, HgI2, and Et2AlI to generate SmI2, see: (c) Girard, P.; Namy, J. L.; Kagan, H. B. J. Am. Chem. Soc. 1980, 102, 2693. (Sm/ICH2CH2I). (d) Imamoto, T.; Ono, M. Chem. Lett. 1987, 501. (Sm/I2). (e) Deacon, G. B.; Forsyth, C. M. Chem. Lett. 1989, 837. (Sm/HgI2). (f) Nishiyama, Y.; Shinomiya, E.; Kimura, S.; Itoh, K.; Sonoda, N. Tetrahedron Lett. 1998, 39, 3705. 330 J. Org. Chem. 2001, 66, 330-333